Mild cognitive impairment A view on grey areas of a grey area diagnosis

Mild cognitive impairment A view on grey areas of a grey area diagnosis Dr Sergi Costafreda Senior Lecturer Division of Psychiatry, UCL Islington Memory Service, C&I NHS FT s.costafreda@ucl.ac.uk London Dementia Strategic Clinical Network 14/06/2017

A grey area: does the label MCI benefit patients? - Harms of diagnosis - There is no cure so aren t we just worrying people unnecessarily? - Can t we just reassure and leave? - There is evidence of significant clinical variability in the use of the MCI label

Petersen 2004 A research diagnosis

The grey zone is between healthy cognitive ageing and dementia (mainly AD) Resnick et al, Neurology 2010;74:807 815

Continuum normal ageing to dementia: MCI is the grey area

MCI responds to a grey zone This development was stimulated first by the clinical awareness of the existence of a grey zone of cognitive impairment that was not captured by any clinical definition and by the rising awareness of dementia as an important area of public health. Further, it was reinforced by the emerging clinical need of something beyond the binary diagnosis of the presence or absence of dementia, which could allow an earlier diagnosis and secondary prevention if new treatments were proved efficacious at these early stages The concept has moved rapidly outside the research field providing clinicians with a helpful intermediate diagnosis, often for watchful waiting. (Petersen et al, 2014)

Extremely prevalent with high risk of dementia

MCI as a clinical diagnosis Benefits: yes for research Benefits for individual patient? Benefits at a social level?

Benefits of MCI diagnosis An early diagnosis is crucial for counseling, for planning treatment and care, and for advance directives. Scientifically, the possibility of making an early (predementia) diagnosis is essential for the clinical evaluation of novel, potentially disease-modifying drugs against AD.

Benefits of MCI diagnosis

Serious harm from diagnosis: suicide mistrust clinical experience: Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment CONCLUSION: Disclosure of a dementia diagnosis does not prompt a catastrophic emotional reaction in most people, even those who are only mildly impaired, and may provide some relief once an explanation for symptoms is known and a treatment plan is developed. Brian D. Carpenter et al. 2008. Journal Am Geriatr Assoc. (But N=90) In population studies (N~100K to 2M): Suicide in dementia is relatively rare (1-2 per thousand), no real info for mild cognitive impairment Suicide in dementia is x3 (LOD) to x10 (EOD) times more likely than in healthy elderly people. Cognitive impairment likely a risk factor in elderly suicide (even if no dementia diagnosis) The EO dementia is very high. The rate for LOD is similar to brain cancer, g-i cancer, liver diseases. Risks factor include depression, psychiatric history, antidepressant/anxiolytic treatment. The highest risk is first 3 months of diagnosis but elevated risk continues beyond that. (Seifreid et al, 2011, Alz & Dem; Erlangsen et al, 2008 Am J Geriatr Psychiatry)

Subjective memory concerns Results: Correlational and regression analyses indicated that subjective memory complaints displayed a poor relationship with objective memory performance. A subsequent discriminant function analysis indicated that subjective memory complaints failed to improve the diagnostic accuracy of MCI and resulted in increased rates of false negative and false positive diagnoses. Conclusion: The results of the present study suggest that a diagnostic criterion of subjective memory complaint reduces the accuracy of MCI diagnosis, resulting in an elevated rate of false positive and false negative diagnoses. The results of this study in conjunction with recent research indicate that a criterion of subjective memory complaint should be discarded from emerging diagnostic criteria for MCI. Lenehan et al. International Psychogeriatrics. 2012, 9:12 pp. 1505-1514

The Nuffield Trust for bioethics report on dementia - After considering benefits/risks of diagnosis People should have access to good quality assessment and support from the time they, or their families, become concerned about symptoms of dementia - This is for dementia, but in my view applies to MCI as well

Criteria and grey areas in clinical definition Depends on patient/informant report (?insight) Preserved independence in functional abilities/ preserved general functional abilities: no hard boundary No prescribed tests/cut-offs: variability in practice (?ACE-R 90, other tests?) No presence of neuropsychiatric symptoms in criteria but frequent subtle changes such as increased reactivity to stress Vega & Newhouse. Curr Psychiatry Rep. 2014 Oct; 16(10): 490.

Preserved functional independence: the grey area at the centre of a grey area diagnosis Very mild problems in instrumental ADL are generally consistent with MCI, whilst basic ADL should be preserved. Petersen 2014 There is a gap here! - Does abandonment of high-end activities count as significant functional impairment? - Does abandonment of driving, or driving only in local areas, count as significant functional impairment? - Does getting some help with finances count as significant functional impairment? Room for subjectivity

Back in the real world CT brain scan was

MCI: syndromic versus aetiological diagnosis The syndromic diagnosis MCI vs normal vs dementia amci vs multidomain MCI vs namci The aetiological diagnosis The subsequent aetiological categories include AD, frontotemporal dementia, vascular cognitive impairment, dementia with Lewy bodies, Parkinson s disease, Huntington s disease, HIV/AIDS, traumatic brain injury and substance abuse

Back in the real world CT brain scan was within normal limits for age What do we do?

Back in the real world CT brain scan showed global involutional changes without lobar predilection within normal limits for age, and small vessel disease. What do we do?

Back in the real world CT brain scan was within normal limits What do we do? A. Discharge with advice B. Advice and review in 1 year C. Neuropsychology D. More scans / other tests

What advice? Findings The prevalence of MCI in adults aged 65 years and older is 10% to 20%; risk increases with age and men appear to be at higher risk than women. In older patients with MCI, clinicians should consider depression, polypharmacy, and uncontrolled cardiovascular risk factors, all of which may increase risk for cognitive impairment and other negative outcomes. Currently, no medications have proven effective for MCI; treatments and interventions should be aimed at reducing cardiovascular risk factors and prevention of stroke. Aerobic exercise, mental activity, and social engagement may help decrease risk of further cognitive decline.

Grey areas: Follow-up Should we follow? Actively recall vs patient/gp to re-refer? When to recall? 6 months-1year? What do we do at meeting? Any cognitive and functional changes? Cognitive testing? When to re-scan?

2010 Neurologists survey in US on MCI When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%) and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of findings (15%). Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other agents (e.g., vitamin E) prescribed less frequently. Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2) motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%). Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer disease (21%); and 3) diagnosis can cause unnecessary worry (20%).

Grey area: depression and memory Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker for future cognitive impairment (amci) http://www.sciencedirect.com/science/article/pii/s1064748116302408 Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer s disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer s disease (P = 0.03). http://bjp.rcpsych.org/content/202/5/329.short Baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7; 95% CI, 1.2-2.3) but not with incident MCI (0.9; 0.7-1.2). Persons with MCI and coexisting depression at baseline had a higher risk of progression to dementia (HR, 2.0; 95% CI, 1.2-3.4), especially vascular dementia (4.3; 1.1-17.0), but not Alzheimer disease (1.9; 1.0-3.6). http://jamanetwork.com/journals/jamaneurology/fullarticle/1542838 So should we treat depression to prevent dementia?

Grey area: depression and memory Assessing Patients with Late-Life Depression for MCI Depressive symptoms have been found to occur in up to 63% of individuals with MCI [41]. Although depression and is frequently associated with MCI and dementia [42 48], the role of depression as a risk factor for MCI and dementia is not fully understood. Differentiation between cause and effect is particularly challenging when assessing patients with late-life depression for MCI since depression by itself is associated with a number of cognitive deficits, including difficulty concentrating, distractibility, forgetfulness, reduced reaction time, memory loss, and indecisiveness [49]. The mechanisms behind the association between depression and cognitive decline are not fully understood and different mechanisms have been proposed [43, 50, 51]. Depression could be a risk factor for dementia, an early dementia symptom, a reaction to cognitive and functional disability, or a symptom of a related risk factor, such as cerebrovascular disease [52]. Treat depression because it s a treatable illness, but relation to dementia and dementia prevention not clear.

Grey area: depression and memory Classically described pseudo-dementia: I don t know - 50% of autopsy-confirmed AD (N=100) had a prior diagnosis of depression, peak incidence 2 y before AD dx Jost and Grossberg in the Journal of the American Geriatric Society, 1996 Depressive symptoms in MCI do no explain memory scores - Depression was independently associated with composite scores of executive functioning and specifically to trails B - Apathy was associated with poorer FAS - Neither apathy nor depression associated with attention, memory, or language - Apathy, but not depression, was associated with greater functional impairment. - Depression and apathy are associated with different aspects of executive functioning in amnestic MCI, which may reflect differing patterns of frontal lobe pathology. Zahodne andtremont. International journal of geriatric psychiatry 28.1 (2013): 50-56.

My take home messages Suspect if people have typical AD symptoms and mild functional changes Important role of mood, anxiety, neuropsychiatric symptoms o o o Much more complex than pseudodementia ; treat depression and let s see often not enough Consider the personal and emotional reaction to diagnosis and prognosis: from denial to catastrophe Suspect AD if there is the general anxiety/depressive prodrome of recent onset Get as much collateral as possible Do not blindly follow scanning, cognitive results